title: GroEL1, a heat shock protein 60 of Chlamydia pneumoniae, induces lectin-like oxidized low-density lipoprotein receptor 1 expression in endothelial cells and enhances atherogenesis in hypercholesterolemic rabbits.
abstract: Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) plays a major role in oxidized low-density lipoprotein-induced vascular inflammation. Chlamydia pneumoniae has been found in atherosclerotic lesions and is related to atherosclerotic pathogenesis, although its specific mechanism remains unknown. This study was conducted to investigate the mechanisms of LOX-1 expression in GroEL1 (a heat shock protein from C. pneumoniae)-administered human coronary artery endothelial cells (HCAECs) and atherogenesis in hypercholesterolemic rabbits. We demonstrated that in the hypercholesterolemic rabbit model, GroEL1 administration enhanced fatty streak and macrophage infiltration in atherosclerotic lesions, which may be mediated by elevated LOX-1 expression. In in vitro study using HCAECs, stimulation with GroEL1 increased TLR4 and LOX-1 expression. Increased LOX-1 expression was downregulated by Akt activation and PI3K-mediated endothelial NO synthase activation. PI3K inhibitor and NO synthase inhibitor induced LOX-1 mRNA production, whereas the NO donor ameliorated the increasing effect of LOX-1 mRNA in GroEL1-stimulated HCAECs. LOX-1 expression was regulated by NADPH oxidase, which mediates reactive oxygen species production and intracellular MAPK signaling pathway in GroEL1-stimulated HCAECs. Treatment with polyethylene-glycol-conjugated superoxide dismutase, apocynin, or diphenylene iodonium significantly decreased GroEL1-induced LOX-1 expression, as did the knockdown of Rac1 gene expression by RNA interference. In conclusion, the GroEL1 protein may induce LOX-1 expression in endothelial cells and atherogenesis in hypercholesterolemic rabbits. The elevated level of LOX-1 in vitro may be mediated by the PI3K-Akt signaling pathway, endothelial NO synthase activation, NADPH oxidase-mediated reactive oxygen species production, and MAPK activation in GroEL1-stimulated HCAECs. The GroEL1 protein of C. pneumoniae may contribute to vascular inflammation and cardiovascular disorders.
authors.affiliation: Division of Cardiology, Taipei Medical University Hospital, Taipei 110, Taiwan.
authors.forename: Feng-Yen
authors.initials: FY
authors.lastname: Lin
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Lin
authors.forename: Chun-Yao
authors.initials: CY
authors.lastname: Huang
authors.forename: Yu-Jia
authors.initials: YJ
authors.lastname: Chang
authors.forename: Nai-Wen
authors.initials: NW
authors.lastname: Tsao
authors.forename: Nen-Chung
authors.initials: NC
authors.lastname: Chang
authors.forename: Keng-Liang
authors.initials: KL
authors.lastname: Ou
authors.forename: Ta-Liang
authors.initials: TL
authors.lastname: Chen
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Shih
authors.forename: Yung-Hsiang
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000328:Adult; D000818:Animals; D050197:Atherosclerosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D045744:Cell Line, Tumor; D018834:Chaperonin 60 / Q000502:physiology*; D023521:Chlamydophila Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D003331:Coronary Vessels / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D004730:Endothelium, Vascular / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D006937:Hypercholesterolemia / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D018836:Inflammation Mediators / Q000009:adverse effects; D008297:Male; D011817:Rabbits; D051127:Scavenger Receptors, Class E / Q000096:biosynthesis* / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D018834:Chaperonin 60; D018836:Inflammation Mediators; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4